tbuckley/cabot-search huggingface dataset:
Trends in Disparities and Transitions of Treatment in Patients With Early Breast Cancer in China and the US, 2011 to 2021
Authors: Jianbin Li, Jifang Zhou, Haibo Wang, Zhenzhen Liu, Zhimin Fan, Yinhua Liu, Cuizhi Geng, Yue Xiao, Zefei Jiang, Yunjiang Liu, Yuhua Song, Min Yan, Qianjun Chen, Ying Lin, Qiang Liu, Feng Jin, Yuee Teng, Peifen Fu, Jianguo Zhang, Zhigao Li, Yiding Chen, Kun Wang, Yongmei Yin, Xiaoming Zha, Haiqing Zhang
Journal: JAMA Network Open (2023)

Breast cancer treatment has profoundly improved in China recently. However, trends in disparities and transitions of treatment in early-stage cancer between China and the US are not well known.
Use of Electronic Nicotine Delivery Systems or Cigarette Smoking After US Food and Drug Administration–Prioritized Enforcement Against Fruit-Flavored Cartridges
Authors: Karin A. Kasza, Cheryl Rivard, Young Sik Seo, Jessica L. Reid, Shannon Gravely, Geoffrey T. Fong, David Hammond, Andrew Hyland
Journal: JAMA Network Open (2023)

Importance The Center for Tobacco Products (CTP) of the US Food and Drug Administration prioritized its enforcement efforts against non–tobacco-, non–menthol- (fruit-) flavored cartridge electronic nicotine delivery systems (ENDS) in February 2020. Objective To evaluate adults’ use of ENDS and cigarette smoking following the CTP’s prioritized enforcement efforts against fruit-flavored cartridge ENDS. Design, Setting, and Participants In this population-based, nationally representative US cohort study, data were collected from the Population Assessment of Tobacco and Health Study from December 2018 to November 2019 (hereafter referred to as 2019) and/or from September 2020 to December 2020 (Adult Telephone Survey, hereafter referred to as 2020). Adults (aged ≥21 years) who used ENDS in the past 30 days and smoked cigarettes in the past 30 days or quit smoking cigarettes in the past year (n = 3173) were evaluated. Data were analyzed from January 1, 2022, to May 2, 2023. Exposure ENDS flavor-device combinations used. Main Outcomes and Measures Outcome measures were cross-sectional prevalence of ENDS flavor-device combinations used in 2019 (n = 2654) and 2020 (n = 519) and longitudinal transitions in cigarette smoking (cessation [no smoking in the past 30 days in 2020 among those who smoked in 2019; n = 876] and relapse [smoking in the past 30 days in 2020 among those who recently quit in 2019; n = 137]) as a function of ENDS flavor-device combination used in 2019. Results The sample in 2019 included 2654 individuals (55% male [95% CI, 53%-58%]). Among those who used ENDS and smoked cigarettes, fruit-flavored cartridge ENDS use decreased from 13.9% (95% CI, 12.1%-15.9%) in 2019 to 7.9% (95% CI, 5.1%-12.1%) in 2020 ( P = .01), whereas fruit-flavored disposable ENDS use increased from 4.0% (95% CI, 3.1%-5.1%) in 2019 to 14.5% (95% CI, 11.6%-18.0%) in 2020 ( P &amp;amp;lt; .001). Patterns were similar among those who recently quit smoking. Neither cigarette cessation nor relapse rates differed between those who used ENDS that were vs were not prioritized for enforcement efforts (cessation: 23.4% [95% CI, 18.1%-29.7%] vs 26.4% [95% CI, 22.4%-30.8%]; adjusted odds ratio, 1.12; 95% CI, 0.57-2.21; relapse: 32.7% [95% CI, 17.1%-53.4%] vs 29.8% [95% CI, 20.3%-41.3%]; adjusted odds ratio, 0.96; 95% CI, 0.24-3.84). Conclusions and Relevance In this nationally representative US cohort study of adults who smoked cigarettes and used ENDS, fruit-flavored cartridge ENDS use was nearly halved between 2019 and 2020. Cigarette cessation and relapse rates did not differ between those who used ENDS targeted by CTP and those who used other ENDS.
Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease
Authors: Erik Schäffner, Mar Bosch-Queralt, Julia M. Edgar, Maria Lehning, Judith Strauß, Niko Fleischer, Theresa Kungl, Peter Wieghofer, Stefan A. Berghoff, Tilo Reinert, Martin Krueger, Markus Morawski, Wiebke Möbius, Alonso Barrantes-Freer, Jens Stieler, Ting Sun, Gesine Saher, Markus H. Schwab, Christoph Wrede, Maximilian Frosch, Marco Prinz, Daniel S. Reich, Alexander Flügel, Christine Stadelmann, Robert Fledrich, Klaus-Armin Nave, Ruth M. Stassart
Journal: Nature Neuroscience (2023)

Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure of denuded axons to immune-mediated damage. Therefore, myelin is widely considered to be a protective structure for axons in multiple sclerosis. Myelinated axons also depend on oligodendrocytes, which provide metabolic and structural support to the axonal compartment. Given that axonal pathology in multiple sclerosis is already visible at early disease stages, before overt demyelination, we reasoned that autoimmune inflammation may disrupt oligodendroglial support mechanisms and hence primarily affect axons insulated by myelin. Here, we studied axonal pathology as a function of myelination in human multiple sclerosis and mouse models of autoimmune encephalomyelitis with genetically altered myelination. We demonstrate that myelin ensheathment itself becomes detrimental for axonal survival and increases the risk of axons degenerating in an autoimmune environment. This challenges the view of myelin as a solely protective structure and suggests that axonal dependence on oligodendroglial support can become fatal when myelin is under inflammatory attack.
Skin Lesions, Foot Drop, and Hand Contractures
Authors: Aidan R. Filley, Saadeddine Saad, Kirstin Altman
Journal: JAMA (2023)

A previously healthy individual in his 20s had 3 months of annular skin lesions, with numbness and paresthesia in the affected areas. Physical examination revealed multiple tattoos, bilateral palpable thickened auricular and ulnar nerves, and claw-hand deformity; test results for rapid plasma reagin, antinuclear antibodies, rheumatoid factor, acid-fast bacilli, mycobacteria, and fungi were negative, and biopsy did not identify Mycobacterium leprae. What is the diagnosis and what would you do next?
Cryptotanshinone‐Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti‐Inflammatory Properties for Wound Healing
Authors: Zongjia Li, Wei Wei, Miaomiao Zhang, Xinyue Guo, Bailin Zhang, Dapeng Wang, Xiue Jiang, Fangxin Liu, Jilin Tang
Journal: Advanced Healthcare Materials (2023)

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.
<i>Notes from the Field:</i> Multistate Outbreak of <i>Escherichia coli</i> O157:H7 Infections Linked to a National Fast-Food Chain — United States, 2022
Authors: Christan Stager, Danielle Donovan, Lauren Edwards, Evelyn Pereira, Laurie Williams, Jennifer Freiman, Colin Schwensohn, Laura Gieraltowski
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In August 2022, the Michigan Department of Health and Human Services alerted CDC to an approximately fivefold increase in regional cases of Escherichia coli O157:H7 infection.Whole genome sequencing was used to characterize isolates from laboratory-confirmed infections in ill persons.Initial patient interviews indicated that many had consumed meals from the same national fast-food chain.Federal, state, and local officials initiated an investigation to identify the outbreak source and prevent additional cases.This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.*CDC defined a case as an E. coli O157:H7 infection with an isolate highly related to the outbreak strain (within 0-2 alleles) by core genome multilocus sequence typing, with illness onset during July 26-August 24, 2022.PulseNet, CDC's national molecular subtyping network for enteric disease surveillance, detected 109 cases from six states, including Michigan (67; 61%), Ohio (24; 22%), Indiana (11; 10%), Pennsylvania (four; 4%), Kentucky (two; 2%) and New York (one; 1%).The median patient age was 22 years (range = 1-94 years), and 49 (45%) were female.Fifty-two (48%) patients were hospitalized, and 13 (12%) developed hemolytic-uremic syndrome, a recognized complication of E. coli O157:H7 infection; no deaths occurred.Hypothesis-generating interviews were conducted with 84 (77%) patients; among these, 70 (83%) reported eating at the same fast-food chain during the week preceding illness onset.Investigation identified 11 restaurant clusters (groups of unrelated ill persons who ate at the same restaurant).Ill persons reported eating food ingredients commonly served together on several menu items.Among 68 patients who provided detailed information, the most commonly reported exposures were beef patties (53; 78%) and romaine lettuce on sandwiches (46; 68%).Early in the investigation, romaine lettuce exposure exceeded 90%, prompting the fast-food chain to remove lettuce in states with outbreak-associated cases.Food handlers infected with the outbreak strain were identified but were unlikely to be the ultimate source.Although ill food handlers might have amplified the outbreak at some locations, many restaurant clusters had no affected food handlers.
Hepatitis C Virus Clearance Cascade — United States, 2013–2022
Authors: Carolyn Wester, Ademola Osinubi, Harvey W. Kaufman, Hasan Symum, William A. Meyer, Xiaohua Huang, William W. Thompson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.
Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer
Authors: Francesca Nardi, Naiara Perurena, Amy E. Schade, Ze-Hua Li, Kenneth Ngo, Elena V. Ivanova, Aisha Saldanha, Chendi Li, Prafulla C. Gokhale, Aaron N. Hata, David A. Barbie, Cloud P. Paweletz, Pasi A. Jänne, Karen Cichowski
Journal: Journal of Clinical Investigation (2023)

Despite the success of KRAS G12C inhibitors in non-small cell lung cancer (NSCLC), more effective treatments are needed. One preclinical strategy has been to co-target RAS and mTOR pathways, however toxicity due to broad mTOR inhibition has limited its utility. Therefore, we sought to develop a more refined means of targeting cap-dependent translation and identify the most therapeutically important eIF4F-translated targets. Here we show that an eIF4A inhibitor, which targets a component of eIF4F, dramatically enhances the effects of KRAS G12C inhibitors in NSCLCs and together these agents induce potent tumor regression in vivo. By screening a broad panel of eIF4F targets, we show that this cooperativity is driven by effects on BCL-2 family proteins. Moreover, because multiple BCL-2 family members are concomitantly suppressed, these agents are broadly efficacious in NSCLCs, irrespective of their dependency on MCL1, BCL-xL, or BCL-2, which is known to be heterogeneous. Finally, we show that MYC overexpression confers sensitivity to this combination because it creates a dependency on eIF4A for BCL-2 family protein expression. Together, these studies identify a promising therapeutic strategy for KRAS-mutant NSCLCs, demonstrate that BCL-2 proteins are the key mediators of the therapeutic response in this tumor type, and uncover a predictive biomarker of sensitivity.
Exposure to Arsenic and Subclinical Cardiovascular Disease in 9- to 11-Year-Old Children, Syracuse, New York
Authors: Brooks B. Gump, Kevin Heffernan, Lynn S. Brann, Dustin T. Hill, Charlotte Labrie-Cleary, Vikrant Jandev, James A. MacKenzie, Nader H. Atallah-Yunes, Patrick J. Parsons, Christopher D. Palmer, Austin A. Roberts, Kestutis Bendinskas
Journal: JAMA Network Open (2023)

Importance Studies in adults have demonstrated associations between arsenic exposure and clinical and subclinical cardiovascular disease (CVD). No studies to date have considered potential associations in children. Objective To examine the association between total urinary arsenic levels in children and subclinical indicators of CVD. Design, Setting, and Participants This cross-sectional study considered 245 children, a subset from the Environmental Exposures and Child Health Outcomes (EECHO) cohort. Children from the Syracuse, New York, metropolitan area were recruited from August 1, 2013, until November 30, 2017, with enrollment throughout the year. Statistical analysis was performed from January 1, 2022, to February 28, 2023. Exposures Total urinary arsenic was measured using inductively coupled plasma mass spectrometry. Creatinine concentration was used to adjust for urinary dilution. In addition, potential exposure routes (eg, diet) were measured. Main Outcomes and Measures Three indicators of subclinical CVD were assessed: carotid-femoral pulse wave velocity, carotid intima media thickness, and echocardiographic measures of cardiac remodeling. Results The study sample included 245 children aged 9 to 11 years (mean [SD] age, 10.52 [0.93] years; 133 [54.3%] female). The geometric mean of the creatinine-adjusted total arsenic level in the population was 7.76 μg/g creatinine. After adjustment for covariates, elevated total arsenic levels were associated with significantly greater carotid intima media thickness (β = 0.21; 95% CI, 0.08-0.33; P = .001). In addition, echocardiography revealed that elevated total arsenic was significantly higher for children with concentric hypertrophy (indicated by greater left ventricular mass and greater relative wall thickness; geometric mean, 16.77 μg/g creatinine; 95% CI, 9.87-28.79 μg/g) relative to the reference group (geometric mean, 7.39 μg/g creatinine; 95% CI, 6.36-8.58 μg/g). With respect to exposure source, significant geographic clustering of total arsenic was found in 1 urban area of Syracuse, New York. Conclusions and Relevance These findings suggest a significant association between arsenic exposure and subclinical CVD in children. Elevated total arsenic levels were found in an area of Syracuse with known elevations of toxic metals from industrial waste, suggesting historical pollution as a possible source. Given the novelty and potential importance of this association, further research is needed to confirm our findings. Any potential effect of urinary arsenic exposure in childhood on actual clinical CVD outcomes in adulthood remains to be determined.
Behavioural Activation versus Treatment as Usual for Depressed Older Adults in Primary Care: A Pragmatic Cluster-Randomised Controlled Trial
Authors: Noortje P Janssen, Peter Lucassen, Marcus J H Huibers, David Ekers, Theo Broekman, Judith E Bosmans, Harm Van Marwijk, Jan Spijker, Richard Oude Voshaar, Gert-Jan Hendriks
Journal: Psychotherapy and Psychosomatics (2023)

Effective non-pharmacological treatment options for depression in older adults are lacking.The effectiveness of behavioural activation (BA) by mental health nurses (MHNs) for depressed older adults in primary care compared with treatment as usual (TAU) was evaluated.In this multicentre cluster-randomised controlled trial, 59 primary care centres (PCCs) were randomised to BA and TAU. Consenting older (≥65 years) adults (n = 161) with clinically relevant symptoms of depression (PHQ-9 ≥ 10) participated. Interventions were an 8-week individual MHN-led BA programme and unrestricted TAU in which general practitioners followed national guidelines. The primary outcome was self-reported depression (QIDS-SR16) at 9 weeks and 3, 6, 9, and 12-month follow-up.Data of 96 participants from 21 PCCs in BA and 65 participants from 16 PCCs in TAU, recruited between July 4, 2016, and September 21, 2020, were included in the intention-to-treat analyses. At post-treatment, BA participants reported significantly lower severity of depressive symptoms than TAU participants (QIDS-SR16 difference = -2.77, 95% CI = -4.19 to -1.35), p &lt; 0.001; between-group effect size = 0.90; 95% CI = 0.42-1.38). This difference persisted up to the 3-month follow-up (QIDS-SR16 difference = -1.53, 95% CI = -2.81 to -0.26, p = 0.02; between-group effect size = 0.50; 95% CI = 0.07-0.92) but not up to the 12-month follow-up [QIDS-SR16 difference = -0.89 (-2.49 to 0.71)], p = 0.28; between-group effect size = 0.29 (95% CI = -0.82 to 0.24).BA led to a greater symptom reduction of depressive symptoms in older adults, compared to TAU in primary care, at post-treatment and 3-month follow-up, but not at 6- to 12-month follow-up.
Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis
Authors: Alan P. Tenney, Silvio Alessandro Di Gioia, Bryn D. Webb, Wai-Man Chan, Elke de Boer, Sarah J. Garnai, Brenda J. Barry, Tammy Ray, Michael Kosicki, Caroline D. Robson, Zhongyang Zhang, Thomas E. Collins, Alon Gelber, Brandon M. Pratt, Yuko Fujiwara, Arushi Varshney, Monkol Lek, Peter E. Warburton, Carol Van Ryzin, Tanya J. Lehky, Christopher Zalewski, Kelly A. King, Carmen C. Brewer, Audrey Thurm, Joseph Snow, Flavia M. Facio, Narisu Narisu, Lori L. Bonnycastle, Amy Swift, Peter S. Chines, Jessica L. Bell, Suresh Mohan, Mary C. Whitman, Sandra E. Staffieri, James E. Elder, Joseph L. Demer, Alcy Torres, Elza Rachid, Christiane Al-Haddad, Rose-Mary Boustany, David A. Mackey, Angela F. Brady, María Fenollar-Cortés, Melanie Fradin, Tjitske Kleefstra, George W. Padberg, Salmo Raskin, Mario Teruo Sato, Stuart H. Orkin, Stephen C. J. Parker, Tessa A. Hadlock, Lisenka E. L. M. Vissers, Hans van Bokhoven, Ethylin Wang Jabs, Francis S. Collins, Len A. Pennacchio, Irini Manoli, Elizabeth C. Engle
Journal: Nature Genetics (2023)

Abstract Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3 . These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.
Preliminary Incidence and Trends of Infections Caused by Pathogens Transmitted Commonly Through Food — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2022
Authors: Miranda J. Delahoy, Hazel J. Shah, Daniel Lowell Weller, Logan C. Ray, Kirk Smith, Suzanne McGuire, Rosalie T. Trevejo, Elaine Scallan Walter, Katie Wymore, Tamara Rissman, Marcy McMillian, Sarah Lathrop, Bethany LaClair, Michelle M. Boyle, Stic Harris, Joanna Zablotsky-Kufel, Kennedy Houck, Carey J. Devine, Carey E. Lau, Robert V. Tauxe, Beau B. Bruce, Patricia M. Griffin, Daniel C. Payne
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Each year, infections from major foodborne pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalizations, and 1,350 deaths in the United States (1). To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites. During 2020-2021, FoodNet detected decreases in many infections that were due to behavioral modifications, public health interventions, and changes in health care-seeking and testing practices during the COVID-19 pandemic. This report presents preliminary estimates of pathogen-specific annual incidences during 2022, compared with average annual incidences during 2016-2018, the reference period for the U.S. Department of Health and Human Services' Healthy People 2030 targets (2). Many pandemic interventions ended by 2022, resulting in a resumption of outbreaks, international travel, and other factors leading to enteric infections. During 2022, annual incidences of illnesses caused by the pathogens Campylobacter, Salmonella, Shigella, and Listeria were similar to average annual incidences during 2016-2018; however, incidences of Shiga toxin-producing Escherichia coli (STEC), Yersinia, Vibrio, and Cyclospora illnesses were higher. Increasing culture-independent diagnostic test (CIDT) usage likely contributed to increased detection by identifying infections that would have remained undetected before widespread CIDT usage. Reducing pathogen contamination during poultry slaughter and processing of leafy greens requires collaboration among food growers and processors, retail stores, restaurants, and regulators.